The Department of Health and Human Services has charged NIH with the mission of developing new medical countermeasures against radiological or nuclear attacks. As part of Project Bioshield, NIH has established a research goal of developing novel radionuclide chelation and decorporation agents for protection against terrorist attacks that involve radiological dispersion devices (ROD), (e.g. dirty bombs) or nuclear detonations. This project will focus on new product development and validation to minimize systemic exposure to radionuclides through novel chelating materials. We propose to develop and validate in animal (in vivo) and human (in vitro) systems new nano-engineered solid sorbents, which have advantages over :heir liquid counterparts in minimizing the absorption of harmful agents into the body and thereby reducing the kidney burden for clearing the radionuclide-bound complex. At the Pacific Northwest National Laboratory (PNNL), a new class of nano-engineered sorbents, self-assembled monolayer on mesoporous supports (SAMMS) materials, has been developed to facilitate the cleanup of radionuclides from complex waste found at the DOE sites. Created by installation of well-designed organic moieties onto the highly ordered mesoporous silica, the SAMMS materials have been demonstrated to be highly effective chelators for Plutonium, neptunium, uranium, americium, radioiodide, cesium and cobalt, all of which can be normally found in nuclear bombs and ROD. The current proposal focuses on extending the application of SAMMS from their proven utility in environmental clean-up to their utility for radionuclide decorporation in humans. The overall goal of this project is to develop and validate SAMMS materials, and evaluate their toxicity (if any) for use in decorporation of humans following acute exposures to radionuclides. The approach focuses on two specific applications: (1) to chelate radionuclides within the gastrointestinal tract in order to limit systemic absorption of ingested materials and (2) to chelate radionuclides in blood that have been absorbed systemically from all routes of exposure (oral, dermal and inhalation). It is anticipated that the proposed experiments will demonstrate that SAMMS can outperform current FDA-approved ehelation therapies by having higher binding affinity and selectivity for the target radionuclides among other non-target species, larger sorption capacity and rapid sorption rate, favorable benefit to risk ratio, and will be available at low costs. Once we have established increased efficacy and safety of SAMMS for radionuclide decorporation, candidate SAMMS will be advanced towards FDA licensure, with a goal of accelerated deployment to protect the public during a nuclear incident that may cause a public health emergency affecting national security.